EP2730586A1 - Complexe de protéine-peptide ayant une action spécifique sur les tissus dermiques, procédé de production et composition pharmaceutique le comprenant - Google Patents
Complexe de protéine-peptide ayant une action spécifique sur les tissus dermiques, procédé de production et composition pharmaceutique le comprenant Download PDFInfo
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- EP2730586A1 EP2730586A1 EP12793726.6A EP12793726A EP2730586A1 EP 2730586 A1 EP2730586 A1 EP 2730586A1 EP 12793726 A EP12793726 A EP 12793726A EP 2730586 A1 EP2730586 A1 EP 2730586A1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/005—Preparations for sensitive skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2/00—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
Definitions
- the invention relates to biologically active substance - protein/polypeptide complex (PPC), prepared from tissues of skin, cerebrum and spinal cord of hoofed farm embryos and intended as a drug substance in medical products stimulating physiological and reparative regeneration in treatment of skin diseases and traumatic injuries and for use in medicine production in aesthetic medicine, beauty therapy, and a process for its preparation.
- PPC biologically active substance - protein/polypeptide complex
- the purpose of this invention was to provide a biologically active substance - direct reparant, which has a tissue-specific regenerative effect on skin tissue.
- the biologically active substance is a PPC with a molecular weight of its constituent protein/polypeptide components ranging from 5 to 200 kDa and the minimum content of medium molecular fraction within the range of 20 to 160 kDa not less than 80%, with a total protein concentration of 0.1 - 4.2 mg / ml, with the solution ultraviolet spectrum absorption peak at wavelength of 215 ⁇ 5 nm within UV-visible range with the wavelength interval of 200 - 500 nm (picture 1) and the presence of specific bands at denaturing gel electrophoresis in 5% polyacrylamide gel (picture 2), and a pharmaceutically acceptable diluent comprising a buffer and excipients - high-molecular compounds belonging to preservatives, detergents, and solubilizers classes in sufficient concentrations.
- a number of preparations are known of protein-peptide nature, made from of raw materials of animal origin, having regenerative activity and used for treatment of skin diseases. The closest from the point of view of the effect achieved include:
- the cardinal object of the invention is production of an effective natural protein/polypeptide complex complying with current international safety requirements to pharmaceuticals.
- the goal set is achieved by the subject group of inventions providing that all conditions of the PPC and the pharmcomposition production are met.
- the subject group of inventions includes the protein/polypeptide complex, a method for producing the same from nerve and skin tissues of hoofed farm embryos at a certain gestation stage, and a pharmcomposition based on this protein/polypeptide complex.
- Another invention of the subject group is a PPC-based pharmaceutical composition making antihypoxic, immunomodulating, tissue-specific reparative effect on skin tissue and mucous membranes, with a rejuvenating effect, prepared as a solution containing, as an active ingredient, a biologically active protein/polypeptide complex under claim 1 in concentration of 0.05 - 2.0 mg/ml, obtained using the method under claim 2, and a pharmaceutically acceptable diluent.
- composition is intended for pharmaceutical and beauty industries, e.g. for parenteral (intradermal, subcutaneous), intranasal or contact administration to mucous membranes and skin.
- parenteral intradermal, subcutaneous
- intranasal intranasal
- contact administration to mucous membranes and skin.
- the ultraviolet spectrum is recorded at wavelengths ranging from 200 to 500 nm: the absorption peak appears at wavelength of 215 ⁇ 5 nm (Picture 1.).
- the constituent protein molecular weight is defined by denaturing gel electrophoresis ( «SDS-Page») in 5% polyacrylamide gel compared to the standard set of marker proteins having molecular weights ranging from 10 kDa to 250 kDa (Picture 2.).
- the complex has the isoelectric point value ranging from 4.2 to 8.4.
- the preparation includes proteins with molecular weights ranging from 5 to 200 kDa, among which at least 70% have molecular weights ranging from 20 to 160 kDa.
- the ultraviolet spectrum is recorded at wavelengths ranging from 200 to 500 nm: the absorption peak appears at wavelength of 215 ⁇ 5 nm (Picture 1.).
- the constituent protein molecular weight is defined by denaturing gel electrophoresis ( «SDS-Page») in 5% polyacrylamide gel compared to the standard set of marker proteins having molecular weights ranging from 10 kDa to 250 kDa (Picture 3).
- the preparation includes proteins with molecular weights ranging from 5 to 200 kDa, among which at least 70% have molecular weights ranging from 20 to 160 kDa.
- the claimed pharmcomposition in form of PPC with a pharmaceutically acceptable diluent helps increase the PPC solution stability and its effect and shelf life.
- Example 1 Method for producing the PPC.
- the presentation is a solution for injection: five 1 ml ampoules (0.1 mg/ml), five 2 ml ampoules (0.1 mg/ml), one 2 ml ampoule (0.2 mg/ml).
- the maximal recommended daily dose is 0.4 mg in case of intralumbar injection and 0.1 mg in case of intravenous injection.
- the original pharmcomposition toxicity study in subchronic experiment was performed in male and female Wistar rats with weights ranging from 200 to 250 g.
- the animals were taken from a nursery.
- the rats were kept in standard conditions in plastic cages 5 animals in each. They were fed with pelletized feed, fresh vegetables, farmer cheese. Water and food were freely available to the animals.
- the vivarium had artificial daylight.
- the air temperature was +18-+20°C.
- a group included 10 animals (5 males and 5 females). The groups were divided as follows:
- Toxicity was assessed against an observation checklist, including:
- Haematologic values in all groups Hb level, red blood cells, white blood cells, thrombocyte counts fell within physiological range.
- Biochemical study the peptide complex taken in test dose did not affect the total plasma protein in experimental animals, which is indicative that the preparation being studied does not adversely affect the protein generating liver function.
- alkaline phosphatase, aspartate and alanine aminotransferase activity was defined in animals' blood plasma.
- mice in all tested groups: in internal organs (liver, kidneys, lungs, heart, spleen, stomach, large and small intestine), internal secretion glands (thyroid, thymus, suprarenal capsules, pancreatic gland), reproductive organs (uterus, ovaries), lymph glands, cerebrum, skin, nose and throat mucosae pathomorphological changes were not detected.
- internal organs liver, kidneys, lungs, heart, spleen, stomach, large and small intestine
- internal secretion glands thyroid, thymus, suprarenal capsules, pancreatic gland
- reproductive organs uterus, ovaries
- lymph glands cerebrum
- skin nose and throat mucosae pathomorphological changes were not detected.
- Study was performed in three weeks old baby chinchilla rabbits weighing 300 to 500 g.
- the preparation was introduced subcutaneously once or twice daily by 0.5 ml (0.05 mg) for two weeks.
- the animals were taken from a nursery.
- the rabbits were kept in standard cages 1 animal in each. They were fed with pelletized feed and fresh vegetables. Water and food were freely available to the animals.
- the vivarium had artificial daylight.
- the air temperature was +18-+20° C.
- Toxicity was assessed against an observation checklist: by survival rate, general appearance, animals' condition and behavior, body weight variation (the rabbits were weighed at the beginning and at the end of the experiment).
- the local irritant effect was defined by changes at visual and histological examination in skin, at sites of injection.
- the experimental data were compared to the reference data and analyzed using statistic software.
- Confocal microscopy epidermic layer and derma itself had a densely packed structure of terminally differentiated cells. Cells have gap junctions.
- Biochemical study blood glucose, alanine and asparaginic aminotransferase activity in all groups fell within physiological range.
- Intracutaneous introduction both in therapeutic and tenfold dose during two weeks did not result in internal organs changes, nor had a toxic effect on hemic system, nor local irritative effect.
- a sample of protein/polypeptide composition was tested, which was transparent liquid, bottled in a sterile dark glass bottle in the amount of 20 ml, containing the substance in 0.1 mg/ml concentration.
- Mutational test on Salmonella typhimurium is a bacterial test system for account of gene mutation to histidine prototrophy when subjected to chemical compounds and/or their metabolites, inducing base substitution or reading frame shift mutations in this organism genome.
- Mutagens inducing base pair substitution are agents inducing base pair substitution mutations in DNA molecule.
- Mutagens inducing genetic code reading frame shift mutations are agents inducing excess or deficiency of single or multiple base pairs in DNA molecule. This method is used to detect the ability of pharmaceutical substances or their metabolites to induce gene mutations in Salmonella typhimurium indicator strains.
- the bacteria are treated with the compound being tested with metabolic activation system (CM+) or without metabolic activation (CM-).
- the number of revertant is counted in different test strains in comparison to the number of spontaneous revertants in negative control options (untreated cultures or solvent treated cultures). If a compound and/or its metabolites being tested are mutagenically active, they will induce back mutations from auxotrophy to histidine prototrophy in histidine-dependent Salmonella typhimurium strains.
- the S9 Wistar male rats liver fraction was used; 5 days prior to sacrifice the rats were subjected to microsomal enzymes inducer introduction - sovol (300 mg/kg, single dose, intraperitoneally).
- ethidium bromide was used (10 ⁇ g/dish) on TA 98 strain at CM+.
- the protein/polypeptide pharmcomposition in form of sterile solution containing 0.1 mg/ml protein was studied: 1.0 and 0.3 ml of original solution per dish and three tenfold dilutions in physiological solution (0.1 ml/dish).
- the substance test doses were 300; 100; 10; 1 and 0.1 ⁇ g/dish.
- the experiment was supported with positive controls using substances inducing mutations in corresponding tester strains, with and without activation conditions.
- sodium azide was used in the amount of 10 ⁇ g/dish for TA 100 strain at CM-; 2,7- diamino -4,9- dioxy -5,10- dioxo-4,5,9,10-tetrahydro-4,9- diazopyrene (DIAM) - ⁇ g/dish for TA 98 strain at CM-; 9-aminoacridine (9AA) - 50 ⁇ g/dish for TA 97 strain at CM-.
- ethidium bromide was used - ⁇ g/dish on TA 98 strain at CM+.
- physiological solution was used (0.1 ml per dish).
- the experiment included options without a metabolic activation system (CM-) and with a metabolic activation system (CM+).
- CM- option direct mutagens effect can be recorded due to the original substance structure activity.
- promutagens i.e. compounds whose effect is related to formation of mutagenic metabolites
- CM- and CM+ options of the substance study analysis findings.
- 2 dishes were used. The mutagenic effect was considered significant if the average number of revertant colonies per dish in the experiment option twice and more exceeded that of the reference option.
- the experiment results were taken into account provided there was a standard response in all options of positive and negative control.
- the number of revertant colonies in control with solvent in options CM- and CM+ fell within the range of spontaneous level variations for these strains.
- the strains response to standard mutagens fell within the range of ordinary levels.
- the studied protein/polypeptide pharmcomposition in all concentrations tested showed no mutagenic effect on TA 100, TA 98 and TA 97 strains in options with and without metabolic activation system.
- CONCLUSION the protein/polypeptide pharmcomposition does not induce gene mutations in Salmonella typhimurium test strains within the entire range of tested concentrations.
- Cytogenetic activity is the ability of a substance to cause structural and numeral chromosomal distortions in somatic and germ cells.
- Micronuclei are small DNA-containing formations consisting of acentric chromosome fragments or ana-telophase laggards. At telophase stage, these fragments can be incorporated into daughter cell nuclei or form single or multiple micronuclei in cytoplasm.
- the study objective was detection and quantitative estimate of cytogenetic (mutagenic) activity of pharmacologic substances in polychromatophil cells (PCC) of mammal marrow.
- the method is based on microscopic recording of cells with micronuclei.
- mice were performed to 2 months old male and female F1 (CBAx C57B16/J) cross-breed mice weighing 18-20 g. Each group included 6 animals. The animals were kept at 12 hours light pattern with free food and water access. Animal experiments for assessment of mutagenic properties of the protein/polypeptide complex with single and five-time dosing were conducted in compliance with official records. Three sessions of experiments were carried out with corresponding controls: therapeutic dose was tested on male animals with a single introduction; subtoxic dose was tested on male animals with a single introduction; therapeutic dose was tested on male animals with a single introduction; subtoxic dose was tested on male animals and female with five-time introduction.
- TD human recommended daily therapeutic dose
- the protein/polypeptide pharmcomposition was recommended to be introduced in the amount of 2 ml at 0.1 mg/ml concentration.
- a human therapeutic dose (TD) including a child's dose, can be 0.05 mg/kg/daily.
- TD human therapeutic dose
- a conversion factor is recommended that takes into account a human or animal body surface area to weight ratio. In our study, it was 8.33. Therefore, the mice TD was approximately 8.33 x human TD (0.42 mg/kg).
- the protein/polypeptide complex was introduced in single dosing to males in doses of 0.2 mg/kg and 0.5 mg/kg.
- Normal saline solvent was used as a negative control. It was introduced intraperitoneally to male and female mice of two reference groups for the same period and in the same amount as to the experimental animals.
- As a positive control 20 mg/kg cyclophosphamide was used, diluted ex tempore in normal saline at a single intraperitoneal introduction 24 hours before sacrifice.
- Marrow cell preparations for micronuclei count were made by a standard method in compliance with guidelines ("Environmental Factors Mutagenic Activity Assessment in Various Mammal Organs Cells by the Micronucleus Method").
- the animals were sacrificed through cervical dislocation 6 hours after the last introduction. Both thigh bones were detached and muscles were removed from them.
- fetal calf serum was used (produced by NPP PanEko).
- the marrow from both thigh bones was washed out into a microtube using a syringe. The suspension was centrifugated at 1,000 rpm for 5 min, the supernatant was removed, and the sediment was carefully resuspended.
- a smear was prepared from a drop of the suspension, which was further air dried out. Then it was fixed with methanol for 3 minutes. Stained according to Romanowsky-Giemsa method. 2,000 polychromatophil cells from each animal were analyzed in encoded preparations. At counting 500 red blood cells, polychromatophilic to normochromatic erythrocytes ratio was defined. Upon analysis completion, the preparations were decoded.
- the positive result criterion is the replicable and probably significant increase of micronuclei polychromatophilic erythrocytes number at least in one group compared to the reference group. Achievement of a positive result is indicative of the fact that the substance induces chromosome damage and/or cell mitotic apparatus disturbances in experimental animals.
- Micronuclei count statistical analysis was performed by comparing experimental series to reference once by X2 criterion; intergroup comparison of polychromatophilic erythrocytes share was carried out using Mann-Whitney test.
- the protein/polypeptide pharmcomposition mutagenic activity was not detected in mice medulla polychromatophilic erythrocytes micronuclei induction test at single and five-time dosings introduced intraperitoneally to male and female mice in 0.42 mg/kg dosage, which in conversion is equivalent to a human therapeutic dose. Also, the mutagenic activity was not detected at single introduction of the protein/polypeptide pharmcomposition to males in maximum possible dosing - 10 mg/kg. The protein/polypeptide complex did not show toxic effect by the "polychromatophilic erythrocytes share" criterion.
- the protein/polypeptide composition does not make a mutagenic effect in Ames test of Salmonella / microsome and in mice medulla polychromatophilic erythrocytes micronuclei induction test in experiments performed in compliance with the Guidelines for Experimental (Non-Clinical) Study of New Pharmaceutical Substances.
- the antistress effect of the claimed preparation was studied on the basis of multivariable techniques for assessment of condition of different components of emotional stress tolerance in rats (behavioral and visceral components). These studies showed that the claimed preparation can increase emotional stress tolerance, i.e. prevent from higher nervous activity and systemic immunity functional disorders and dysmetabolisms of cardiac function.
- the most effective dosage was 20 ⁇ l per 100 g of a rat weight, which corresponds to 2 ml per 1 injection for a human.
- the burn degree was regulated by the time of electrode exposure which was 3 to 15 seconds.
- the rats were sacrificed on the 3, 7, 14, 23, 30 and 60 th day upon making a burn; the burnt tissues were subjected to histological examination. Macroscopic observation showed that immediately after the burn, a sharply marginated dry, dense, off white-grey, with patches of cyanotic color eschar appears on skin. The skin around the thermal influence area becomes oedematous. A pink crown appears around the eschar.
- the thermal burn area examination showed no visual difference from the subjacent tissues in the pharmcomposition group, there was no qualitative morphological change compared to normal skin tissue.
- hypertrophic cicatrization was observed with a protuberance over the subjacent skin cover.
- Morphological examination showed increased content of destructured collagen in all skin layers.
- Immunomodulatory properties of the PPC produced by the same method as in Examples 1 and 2 were determined by macrophage activation of Wister rats peritoneal exudate in experiments in vitro on enhancement of the enzyme activity in reduction of nitro-blue tetrazolium to diphormazane (NBT-test) and on enhancement of the phagocytic activity to E.Coli.
- Macrophage content in tissue exudate of all cells was 25-35%. Determination of the enzymatic activity of rat peritoneal exudate macrophages was defined by spectrophotometry using reduction of the nitro blue tetrazolium into diphormazane.
- the resulting slurry in the amount of 0.2 ml was applied to an 18 x 18 mm piece of glass and incubated at +37 °C for 30 min in an atmosphere containing 5% carbon dioxide (CO 2 ) for attaching macrophages to the glass.
- CO 2 carbon dioxide
- the latter was rinsed three times in cups containing Hanks medium.
- 0.2 ml of E.Coli suspension with concentration of 20 x 10 6 cells / ml was added and incubated under the same conditions for 45min. Subsequently, the glass was rinsed again three times, fixed with methanol and stained according to Romanowsky-Giemsa method.
- Phagocytosis index was determined using the following formula: PI (0 + 2,5 n + 6T + 9p + 10P) / number of cells with 0 - the number of cells not phagocytizing E.Coli; n - the number of cells that have phagocytized 1-4 E.Coli cells; T - the number of cells that have phagocytized 5-7 E.Coli cells, P - the number of cells that have phagocytized 8-9 E.Coli cells; R - number of cells that have phagocytized more than 10 E.Coli cells. Macrophages were identified by non-specific esterase staining.
- Wister rats peritoneal exudate macrophage activation level in experiments in vitro in the preparation group was significantly exceeding that of the reference group with p ⁇ 0.05 (12 times) in study of enzyme activity increase in reduction of nitro-blue tetrazolium into diphormazane (NBT-test) and 8 times (p ⁇ 0.01) in increase of phagocytic activity for E.Coli.
- the preparation was introduced intracutaneously, symmetrically, directly into the wrinkle lines in 10 points on each side, 0.2 ml per point. Injections were made symmetrically chequerwise, at equal intervals from each other.
- the face skin acquired a fresh natural look; its tonicity and elasticity were restored.
- the external canthus lines had virtually disappeared and on the forehead and nasal bridge have significantly smoothed.
- gray hair amount has decreased.
- the result over the coming months was stable; the patient was satisfied with the treatment, remarking a significant decrease of gray hair and increase of hair thickness. Therefore, the proposed pharmcomposition allows for improving the efficiency of skin aging treatment due to quick restoration of its fibroarchitecture and systemic immunoregulatory effect on the entire organism.
- the attached pictures 1-4 show the complex testing and study results on the invention.
- Picture 1 shows the protein-polypeptide complex spectrum pattern in the UV-visible range of the spectrum obtained according to Example 1.
- the protein-polypeptide complex produced according to the claimed method under Example 1 is characterized by the absorption peak at wavelength of 215 ⁇ 5 nm within UV-visible range.
- Picture 2 shows denaturing gel electrophoresis of the Example 1.
- Picture 3 shows Example 2 protein-polypeptide complex UV-spectrum. According to this picture, in the range of 200 to 500 nm wavelengths, the absorption peak is observed at wavelength of ⁇ (215 ⁇ 5) nm.
- Picture 4 shows denaturing gel electrophoresis of the Example 2.
- the invention allows for creation of a biologically active substance with enhanced properties and high biological activity having reparative and regenerative tissue-specific and rejuvenating action on skin tissue, and for developing a method for producing the same by extracting biologically active protein-polypeptide complex from nervous and skin tissues ungulate farm embryos which is solved by a selected set of procedures and modes. Particularly important was to determine the optimal gestation timing of fetal skin and nervous tissues, as well as a set of reagents, their dosage, extraction and buffering regimes, to maintain effective concentration ratios of proteins, polypeptides, and nucleotides fixed evolutionarily and defining the biological activity of the complex, providing reparative and regenerative tissue-specific and rejuvenating effect.
- the invention is intended for use in chemical and pharmaceutical industries, medicine and cosmetics, is related to biologically active substance-protein/polypeptide complex derived from embryonic neural and skin tissues of hoofed farm animals, having antihypoxic, rejuvenating effect, stimulating physiological and reparative regeneration of skin tissue, for use in production of medicines and cosmetics for skin diseases, aesthetic medicine, and cosmetology.
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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RU2011121685/10A RU2460736C1 (ru) | 2011-05-30 | 2011-05-30 | Белково-полипептидный комплекс (бпк), обладающий тканеспецифическим репаративным и омолаживающим действием на кожную ткань, способ получения белково-полипептидного комплекса, обладающего тканеспецифическим репаративным и омолаживающим действием на кожную ткань, и фармацевтическая композиция на основе бпк, обладающая антигипоксическим, иммуномодулирующим, тканеспецифическим репаративным действием на кожную ткань и слизистые оболочки, с омолаживающим эффектом |
PCT/RU2012/000140 WO2012166005A1 (fr) | 2011-05-30 | 2012-02-28 | Complexe de protéine-peptide ayant une action spécifique sur les tissus dermiques, procédé de production et composition pharmaceutique le comprenant |
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EP2730586A1 true EP2730586A1 (fr) | 2014-05-14 |
EP2730586A4 EP2730586A4 (fr) | 2014-12-03 |
EP2730586B1 EP2730586B1 (fr) | 2018-04-11 |
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EP12793726.6A Not-in-force EP2730586B1 (fr) | 2011-05-30 | 2012-02-28 | Complexe de protéine-polypeptide provenant de tissus d'embryons d'ongulés , procédé de production et composition pharmaceutique le comprenant |
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EP (1) | EP2730586B1 (fr) |
RU (1) | RU2460736C1 (fr) |
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Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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RU2577135C2 (ru) * | 2014-07-01 | 2016-03-10 | Диамондзлите Лимитед | Способ лечения пациентов с онкологическими заболеваниями кожи при развитии неопластических процессов кожной ткани, таких как меланома, базально-клеточный, плоскоклеточный рак (варианты) |
RU2586286C2 (ru) * | 2014-10-16 | 2016-06-10 | ДИАМОНДЗЛИТЕ ЛИМИТЕД Тридент Чамберс | Применение для лечения и профилактики атеросклероза белково-пептидного комплекса (далее-бпк), полученного из эмбриональной нервной ткани или из быстрозамороженного эмбрионального мозга сельскохозяйственных копытных животных, влияющего на обратный транспорт холестерина из сосудистой стенки и профиль активации моноцитов у пациентов с выраженным атеросклерозом магистральных сосудов или с предрасположенностью к сердечно-сосудистым заболеваниям и способ профилактики и лечения пациентов с атеросклерозом артериальных сосудов и с заболеваниями, вызванными атеросклерозом магистральных и периферических сосудов головного мозга, сердца, сосудов нижних конечностей и аорты (два варианта) |
RU2619208C2 (ru) * | 2015-10-08 | 2017-05-12 | ДИАМОНДЗЛИТЕ ЛИМИТЕД Тридент Чамберс | Способ профилактического лечения при развитии неопластических процессов кожной ткани, таких как меланома, базально-клеточный рак, плоскоклеточный рак |
CN113603762B (zh) * | 2021-08-20 | 2023-06-27 | 吉林农业大学 | 一种花马杂交鹿鹿角盘活性肽及其制备方法和应用 |
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US20060058238A1 (en) * | 2004-09-15 | 2006-03-16 | Lee Laurent-Applegate | Fetal skin cell protein compositions for the treatment of skin conditions, disorders or diseases and methods of making and using the same |
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FR2413912A1 (fr) | 1978-01-10 | 1979-08-03 | Bontemps Raymond | Medicaments a base de substances d'origine foetale et leur procede preparation |
FR2530466A1 (fr) | 1982-07-21 | 1984-01-27 | Hecmati Michel | Gel anti-ride, produit et procede |
UA35631C2 (uk) | 1996-07-25 | 2001-04-16 | Дмитро Бориславович ШОРОХ | Спосіб виготовлення біологічно активних препаратів з ембріональних тканин |
RU2144815C1 (ru) | 1996-12-24 | 2000-01-27 | Общество с ограниченной ответственностью Научно-производственный центр "Сибирская природная косметика" | Способ получения регенерирующего косметического крема для ухода за кожей |
RU2142784C1 (ru) | 1997-04-03 | 1999-12-20 | Закрытое акционерное общество Научно-производственный центр "Сибирская природная косметика" | Косметическое средство для ухода за кожей "гармония" |
RU2142785C1 (ru) * | 1997-04-03 | 1999-12-20 | Закрытое акционерное общество Научно-производственный центр "Сибирская природная косметика" | Косметическое средство для ухода за кожей "гармония-n" или "гармония-r" |
EA003301B1 (ru) * | 2000-04-28 | 2003-04-24 | Научно-Производственное Республиканское Унитарное Предприятие "Диалек" | Способ получения лекарственного средства из ткани мозга эмбрионов животного и фармакологическая композиция на его основе |
RU2189257C1 (ru) | 2001-10-10 | 2002-09-20 | Хуснутдинов Анис Хатыпович | Биоматериал аллоплант для регенеративной хирургии |
RU2229886C1 (ru) | 2002-11-13 | 2004-06-10 | Открытое Акционерное Общество "Фаберлик" | Средство, нормализующее обмен веществ в тканях кожи |
RU2289417C1 (ru) | 2005-04-15 | 2006-12-20 | Равиль Шамилевич Мирхайдаров | Способ биологического омоложения кожи |
RU2355405C2 (ru) | 2007-05-17 | 2009-05-20 | Михаил Аркадьевич Шурдов | Пептидный экстракт плаценты и способ его изготовления |
WO2009088314A1 (fr) | 2007-12-29 | 2009-07-16 | Zakritoe Aktcionernoe Obschestvo "Pharm-Sintez" | Procédé de production d'un complexe biologiquement actif présentant une activité neurorégénérative et neuroprotectrice |
WO2010007620A1 (fr) * | 2008-07-13 | 2010-01-21 | Delapharm Ltd. | Composition pharmaceutique comprenant de l’extrait de cerveau porcin |
JP5573985B1 (ja) | 2013-01-31 | 2014-08-20 | 住友大阪セメント株式会社 | 光変調器 |
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2011
- 2011-05-30 RU RU2011121685/10A patent/RU2460736C1/ru active
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- 2012-02-28 WO PCT/RU2012/000140 patent/WO2012166005A1/fr active Application Filing
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US20060058238A1 (en) * | 2004-09-15 | 2006-03-16 | Lee Laurent-Applegate | Fetal skin cell protein compositions for the treatment of skin conditions, disorders or diseases and methods of making and using the same |
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WO2012166005A1 (fr) | 2012-12-06 |
RU2460736C1 (ru) | 2012-09-10 |
EP2730586B1 (fr) | 2018-04-11 |
EP2730586A4 (fr) | 2014-12-03 |
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